The Dawn of Oral PCSK9 Inhibitors: A New Era in Cholesterol Management
The landscape of cardiovascular disease prevention is poised for a significant shift. Recent publication of the Phase 3 CORALreef Lipids trial in The New England Journal of Medicine showcases the remarkable efficacy of enlicitide decanoate, an investigational oral PCSK9 inhibitor developed by Merck. This breakthrough offers a potentially game-changing alternative to existing injectable PCSK9 inhibitors, promising improved patient adherence and broader access to critical lipid-lowering therapy.
Understanding the Impact: Beyond LDL-C Reduction
The CORALreef Lipids trial, involving 2904 participants at risk of or with established atherosclerotic cardiovascular disease (ASCVD), demonstrated a striking 57.1% reduction in low-density lipoprotein cholesterol (LDL-C) with enlicitide compared to a 3.0% increase with placebo. This primary endpoint achievement is substantial, but the benefits extend beyond LDL-C. The study also revealed significant reductions in non–high-density lipoprotein cholesterol (non–HDL-C), apolipoprotein B (ApoB) and lipoprotein(a) [Lp(a)].
Convenience and Adherence: The Oral Advantage
Currently available PCSK9 inhibitors require injection, which can be a barrier to adherence for some patients. Enlicitide’s oral formulation addresses this challenge, potentially leading to more consistent medication use. As Joseph Saseen, PharmD, BCPS, BCACP, CLS, professor at the University of Colorado Anschutz Skaggs School of Pharmacy and Pharmaceutical Sciences, noted, the oral route “can fit the scheme of how patients usually take their maintenance medications.”
The Role of Pharmacists in a Changing Landscape
The introduction of oral PCSK9 inhibitors will likely expand the role of pharmacists in cardiovascular care. Pharmacists will be crucial in educating patients about the benefits of enlicitide, monitoring for potential drug interactions, and ensuring optimal adherence. Ann Marie Navar, MD, PhD, of UT Southwestern Medical School, highlights that enlicitide offers “a great option for patients who are above goal and demand additional nonstatin therapy.”
Accelerated Approval Pathway and Future Outlook
Recognizing the potential public health impact, the FDA has granted enlicitide a national priority voucher, expediting the review and approval process. This voucher program is designed to incentivize the development of therapies addressing unmet medical needs. The potential for faster approval underscores the urgency of addressing the ongoing cardiovascular epidemic.
Frequently Asked Questions
What are PCSK9 inhibitors?
PCSK9 inhibitors are a class of drugs that lower LDL-C levels by blocking the PCSK9 protein, which prevents the liver from removing cholesterol from the blood.
Who is likely to benefit from enlicitide?
Individuals with a history of ASCVD or those at high risk for a first event, particularly those who haven’t reached their LDL-C goals with statins, are likely candidates for enlicitide.
How does enlicitide compare to injectable PCSK9 inhibitors?
Enlicitide is an oral medication, offering a more convenient administration route compared to injectable PCSK9 inhibitors.
The arrival of enlicitide represents a significant step forward in the fight against cardiovascular disease. Its oral formulation, coupled with its impressive lipid-lowering effects, has the potential to transform treatment paradigms and improve outcomes for millions of patients at risk.
References:
- Navar AM, Mikhailova E, Catapano AL, et al. A placebo-controlled trial of the oral PCSK9 inhibitor enlicitide. N Engl N Med. 2026;394:529-539. Doi:10.1056/NEJMoa2511002
- Halpern L. New enlicitide decanoate data show significant LDL-C reductions in at-risk patients. Pharmacy Times. Published November 19, 2025. Accessed February 5, 2026. https://www.pharmacytimes.com/view/new-enlicitide-decanoate-data-show-significant-ldl-c-reductions-in-at-risk-patients
- Saseen JJ, Halpern L. Expert: Debunking cholesterol myths and the rise of oral PCSK9 inhibitors. Pharmacy Times. Published February 4, 2026. Accessed February 5, 2026. https://www.pharmacytimes.com/view/expert-debunking-cholesterol-myths-and-the-rise-of-oral-pcsk9-inhibitors
- Navar AM, Halpern L. Q&A: How oral PCSK9 inhibitors will revolutionize pharmacists’ role in cholesterol control. Pharmacy Times. Published January 22, 2026. Accessed February 5, 2026. https://www.pharmacytimes.com/view/q-a-pharmacists-role-in-the-era-of-oral-pcsk9-inhibitors-for-cholesterol-control
- Halpern L. FDA grants national priority vouchers to enlicitide decanoate, sacituzumab tirumotecan. Pharmacy Times. Published January 7, 2026. Accessed February 5, 2026. Https://www.pharmacytimes.com/view/fda-grants-national-priority-vouchers-to-enlicitide-decanoate-sacituzumab-tirumotecan
Desire to learn more about cardiovascular health? Explore our other articles on cholesterol management and ASCVD prevention.
